Doxorubicin is a current chemotherapeutic drug used in the treatment of blood cancers and various carcinomas, including breast cancer. Doxorubicin is known to have effects on myeloid populations, particularly myeloid derived suppressor cells (MDSCs). Several lines of evidence suggest that chemotherapy-treated tumors may become less susceptible to immune attack, therefore, we wanted to investigate the effects of doxorubicin on carcinoma cells, exploring whether they become more immune suppressive after treatment.
We used the 4T1 murine mammary carcinoma model to investigate the effects of doxorubicin treatment both in vitro and in vivo. We found that treatment with low concentrations of doxorubicin in vitro caused 4T1 cells to produce immuno-suppressive factors, which inhibited proliferation of T lymphocytes in vitro. Doxorubicin treatment by intraperitoneal administration into 4T1-burdened BALB/cByJ mice showed a significant decrease in tumour load. There was also a decrease in myeloid populations within the lymph node and the spleen. The response of these tumors to immunotherapy will be investigated.
These findings have implications for breast cancer patients receiving doxorubicin as chemotherapy. Further research will help strengthen our understanding of the impact of doxorubicin on the immune system, with the goal to improve current therapies available and work towards better cancer immunotherapies.
Contact Author: cgilfillan@malaghan.org.nz
This research was funded by a grant from the Cancer Society of NZ. CG was supported by a PhD scholarship from University of Otago.